Targeting the Autonomic Nervous System for Risk Stratification, Outcome Prediction and Neuromodulation in Ischemic Stroke

Abstract

Ischemic stroke is a worldwide major cause of mortality and disability and has high costs in terms of health-related quality of life and expectancy as well as of social healthcare resources. In recent years, starting from the bidirectional relationship between autonomic nervous system (ANS) dysfunction and acute ischemic stroke (AIS), researchers have identified prognostic factors for risk stratification, prognosis of mid-term outcomes and response to recanalization therapy. In particular, the evaluation of the ANS function through the analysis of heart rate variability (HRV) appears to be a promising non-invasive and reliable tool for the management of patients with AIS. Furthermore, preclinical molecular studies on the pathophysiological mechanisms underlying the onset and progression of stroke damage have shown an extensive overlap with the activity of the vagus nerve. Evidence from the application of vagus nerve stimulation (VNS) on animal models of AIS and on patients with chronic ischemic stroke has highlighted the surprising therapeutic possibilities of neuromodulation. Preclinical molecular studies highlighted that the neuroprotective action of VNS results from anti-inflammatory, antioxidant and antiapoptotic mechanisms mediated by α7 nicotinic acetylcholine receptor. Given the proven safety of non-invasive VNS in the subacute phase, the ease of its use and its possible beneficial effect in hemorrhagic stroke as well, human studies with transcutaneous VNS should be less challenging than protocols that involve invasive VNS and could be the proof of concept that neuromodulation represents the very first therapeutic approach in the ultra-early management of stroke.

Targeting autonomic nervous system as a biomarker of well-ageing in the prevention of stroke

“…The predictive power of ANS activity for cardiovascular diseases may lead to a large utilization of autonomic modulation in preventing the occurrence of ischemic and hemorrhagic stroke and limiting their severity ( Carandina et al, 2021 ). We may well have the age of our autonomic nervous system and we can enhance its protective activity through physical exercise or, if is difficult to exercise, through tVNS.…”

“…Autonomic nervous system activity and traditional risk factors are strongly related as ANS imbalance contributes to the creation of a pre-pathological milieu of composite risk factors, such as hypertension, diabetes or atrial fibrillation and alterations of endothelial homeostasis in favor of pro-thrombotic/proinflammatory state, eventually leading to increased risk of stroke ( Saeed et al, 2005 ; Bäck et al, 2019 ; Carandina et al, 2021 ). Thus ANS monitoring is of importance in stroke prevention focusing on the imbalance characterized by a decrease in parasympathetic activity and a concurrent increase in sympathetic activity.…”

“…Endothelium health is thus strongly dependent on parasympathetic activity. Rebalancing autonomic activity through VNS attenuates this dysfunction and protects from stroke ( Carandina et al, 2021 ).…”

Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes

“…Animal models of ischemic stroke showed elevated numbers of activated mast cells, and activation of mast cells can increase angiogenesis by increasing proinflammatory monocyte responses, 32,33 which in turn can promote the progression of diabetes and increase risk of ischemic stroke. 4,34 Our work may help guide further research into how immune cell changes, immune responses, and inflammatory events interact to contribute to ischemic stroke in T2DM patients.…”

Improving Cardiovascular Outcomes: The Era of Personalized Therapy in Atherosclerosis

“…40% of the mortality in Europe, with atherosclerosis being a major contributor to case fatality [ 1 ]. Progression of atherosclerotic lesions is a time-dependent condition leading to life-shortening clinical events, such as myocardial infarction, ischemic stroke, claudication and renal failure, or intestinal ischemia [ 2 , 3 , 4 ].…”